tbuckley/cabot-search huggingface dataset:
Abstract 10362: Prognostic Value of Assessing Left Atrial Remodeling in Predicting Cardiac Events Following Transcatheter Aortic Valve Replacement
Authors: Hideaki Kanzaki, Yuki Irie, takashi kakuta, Atsushi Okada, Makoto Amaki, Kensuke Takagi, Naonori Kawamoto, Tomoyuki Fujita, Chisato Izumi
Journal: Circulation (2022)

Introduction: Left atrial (LA) volume indexed to body surface area (LAVi) is an established predictor of cardiovascular risk. The ratio of LAVi to mitral annular velocity during atrial contraction (LAVi/a') has emerged as a superior indicator to LAVi in assessing LA remodeling. However, the significance of calculating LAVi/a' in patients undergoing transcatheter aortic valve replacement (TAVR) has not been fully investigated. Hypothesis: The assessment of LA remodeling using LAVi/a' in patients with severe aortic stenosis (AS) provides crucial prognostic information after TAVR. Methods and Results: This study was composed of 486 patients with sinus rhythm (aged 83 ± 5 years; 175 men, 311 women) who underwent TAVR. Transthoracic echocardiography, including tissue Doppler, was performed before TAVR. Patients were divided into two groups according to the median LAVi/a'. The Kaplan-Meier method showed more adverse cardiac events (cardiac death and heart failure hospitalization) in the group with LAVi/a' above the median (log-rank test, P = 0.030). Multivariate Cox regression analysis adjusted for age and sex revealed that LAVi/a' was an independent prognostic parameter (hazard ratio, 1.058; P = 0.001). Conclusions: Patients with AS who have advanced LA remodeling are more likely to develop the adverse cardiac events even after successful TAVR. LAVi/a' is useful for predicting the cardiac events following TAVR and may be superior to LAVi.
Abstract 10397: Unbiased Cluster Modelling for Uncovering Natural Distribution of Doppler Derived Diastolic Variable Response to Exercise Among Patients Referred to Exercise Echocardiography
Authors: Alaa M Omar, Swiri Konje, Loba Alam, Kruti Gandhi, Errol Moras, Brissete Mancero, Elizabeth Zipf, David Meister, Maria Pena, Christopher Perez Lizardo, Ga Hee Kim, Ga Hee, Joseph Elias, Edgar Argulian
Journal: Circulation (2022)

Introduction: Exercise-induced diastolic dysfunction is associated with poor prognosis. Hypothesis: We studied diastolic response to exercise based on the natural distribution of Doppler variables and its relationship to adverse outcomes. Methods: In a retrospective study, 813 patients referred for exercise echocardiography (ExE) for ischemia assessment were included (Age: 58±13 years, 57% females, EF:60±7%). A 2-step unsupervised cluster model was constructed using resting and post-exercise tissue Doppler early diastolic mitral annular velocity, post-exercise pulsed Doppler-derived mitral inflow velocity in early and late diastole, and post-exercise tricuspid regurgitation velocity. Clusters were compared for a composite outcome (death, cardiac rehospitalization, acute coronary syndrome, and need for future ischemia testing). Results: Exercise-induced ischemia occurred in 116(14%). The composite outcome occurred in 196(24%) patients over a median follow-up of 3.2 years. The model yielded 2 clusters labelled low and high risk for the composite outcome, Figure 1 A,B). Compared to the low risk cluster, patients in the high risk cluster were older, had more risk factors and comorbidities, worse exercise performance, worse resting and exercise diastolic variables, and more ischemic ExE. After stratification for ischemia, clusters resulted in significant separation of risk for the outcome, regardless of the presence or absence of ischemia (Figure 1 C,D). These findings persisted after multivariate adjustment. Conclusions: In patients referred to ExE for assessment of ischemia, diastolic response to exercise involves complex interactions among diastolic variables. Appreciation of such complexity seems to add prognostic value beyond ischemia, suggesting a need for novel approaches for characterization of the natural distribution of diastolic variables, such as computational unbiased clustering.
Abstract 10390: Using a Trial Modelling Framework to Emulate a Target Trial Evaluating Revascularisation Strategies in Patients With Heart Failure
Authors: Suraj Pathak, Florence Lai, Joanne Miksza, Mark Petrie, Gavin Murphy
Journal: Circulation (2022)

Introduction: We developed a novel trial modelling framework which utilises real world data to emulate a target trial and estimate key parameters to support trial planning. We applied this framework using the UK Hospital Episode Statistics (HES), which captures all admissions at NHS hospitals in England, and reported the findings of an emulated target trial evaluating revascularisation strategies in heart failure (HF) patients with coronary artery disease. Methods: Phenotyping algorithms derived from the target trial protocol were applied to HES, to identify HF patients who had coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Trial participants are often different from the target trial population due to voluntary basis of participation. The HES-derived cohort was matched on baseline features (age, gender, comorbidities) to an existing trial (STICH) which targeted the same high-risk population, so that the matched cohort mimics a likely trial population. Treatment effects were estimated using instrumental variable analysis (IVA) and meta-learning models to adjust for confounding. Results: A total of 13,519 HF patients undergoing revascularisation during April 2009 and March 2015 met the eligibility criteria. This HF patient cohort was matched with the STICH cohort, resulting in 2046 patients in the study cohort. The 5-year composite outcome of all-cause mortality or cardiovascular hospitalisation was observed in 51.1% of HF patients who had CABG and 70.0% in those who had PTCA. IVA showed that CABG was associated with a lower risk of the composite outcome (risk difference -16.2%, 95%CI: -20.6% to -11.8%). This was consistent with the treatment effects derived from other machine learning models. Our analyses also identified a trend in greater treatment effects being observed in the matched cohort than unmatched cohort. This suggests that a clinical trial may over-estimate treatment effects when compared to the actual treatment benefit observed in clinical practice. Conclusions: The framework provides a structured process to emulate a trial and anticipate findings of the trial. Our analyses showed that CABG is associated with a greater long-term benefit in HF patients requiring revascularisation.
Abstract 10406: Longitudinal Trends in Cardiovascular Complications Among Patients Hospitalized for Covid-19 Infection: A National Multi-Center Analysis
Authors: Eric J Hall, Sandeep R Das, Colby Ayers, Steven M Bradley, Mitchell Elkind, Jennifer L Hall, Ahmed A Kolkailah, Pratheek Mallya, David Morrow, Fatima Rodriguez, Gregory A Roth, Christine Rutan, Laura Stevens, Tracy Y Wang, Jason Walchok, Joseph H Williams, James A De Lemos
Journal: Circulation (2022)

Introduction: COVID-19 is associated with multiple cardiovascular disease (CVD) complications, while pre-existing CVD and CVD risk factors increase the risk of severe COVID. The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of CVD complications or risk factor profiles of hospitalized patients have changed over the course of the pandemic. Methods: We analyzed the AHA COVID-19 CVD registry, a national multi-center registry of hospitalized adults with active COVID-19 infection. Data from March 2020 were excluded, and subsequent periods from April 2020 to December 2021 were divided into 3-month epochs. Trends in CVD risk factors and CVD outcomes, including a composite primary outcome of CVD death, cardiogenic shock, new heart failure (HF), stroke, and MI, were evaluated across epochs. Results: 39,961 patients were included. Mean age was 62±18 years during the first epoch and remained consistent through March 2021, after which it decreased and remained stable (55±18 years by the last epoch; p trend &lt;0.001). Patients admitted later in the pandemic were more likely to be obese and less likely to have existing CVD (p trend &lt;0.001 for each). The incidence of the primary outcome (Figure) increased from 7.2% to 9.8% from the first to the last epoch (p trend &lt;0.001). This was driven by an increase in the diagnosis of MI and stroke. Diagnosed pulmonary embolism also rose from 1.9% to 4.7% over the study period (p trend &lt;0.001). There was no consistent trend in the rates of new HF, cardiogenic shock, or CVD mortality, all of which were uncommon, occurring in ≤2% of the overall study population. Conclusions: Despite a shifting risk factor profile towards a younger population with lower rates of established CVD, the incidence of diagnosed CVD complications among patients hospitalized for COVID-19 increased over the course of the pandemic.
Abstract 10336: Phase 3 Anticancer Agent, RRx-001, Ameliorates Hypoxia-Induced Pulmonary Hypertension
Authors: Pedro Cabrales, Tony Reid, Scott Caroen, Bryan Oronsky
Journal: Circulation (2022)

Introduction: The hallmark features of pulmonary artery hypertension (PAH), for which hypoxia is a trigger, are vascular remodeling, elevated pulmonary blood pressure, oxidative stress, and right ventricular hypertrophy. RRx-001 is a minimally toxic Phase 3 anticancer agent with anti-oxidative, anti-inflammatory, nitric oxide-donating, and anti-proliferative properties. This study aimed to investigate the effect of RRx-001 on intermittent hypoxia-induced PAH in rats. Hypothesis: RRx-001 attenuates PAH Methods: Male Wistar rats (180-220 g) were divided into four groups (n=6 per group): normoxic control, hypoxic with vehicle treatment (2 weeks breathing an atmosphere containing 10% oxygen), hypoxic treated with oral endothelin-1 receptor inhibitor, bosentan, 50 mg/kg per day for 2 weeks during hypoxia and one intravenous dose of 5mg/kg RRx-001 given the day before the start of the hypoxia. After sacrifice, hearts and lungs were removed and harvested for analyses. Results: RRx-001 and bosentan, separately, significantly attenuated hypoxia-induced increases in right ventricular systolic pressure and right ventricular hypertrophy in PAH rats vs. vehicle. RRx-001 and bosentan, separately, also significantly decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats and the wall thickness/external diameter ratio of the pulmonary arteries vs. vehicle. Conclusions: RRx-001 significantly reduced right ventricular systolic pressure and pulmonary remodeling in a rat model of PAH, which potentially makes it a new therapeutic option for this dread disease. As a next step, combination of RRx-001 and bosentan will be attempted.
Abstract 10408: Insulin Resistance in Type 2 Diabetes is Moderated by Saturated Fatty Acids
Authors: Alice M Mezincescu, Amelia Rudd, Lesley Cheyne, Graham Horgan, Sam Philip, Donnie Cameron, Luc van Loon, Philip Whitfield, Rachael Gribbin, Mirela Delibegovic, Barbara Fielding, Stuart Gray, Anke Henning, Dana K Dawson
Journal: Circulation (2022)

Background: Increased intramyocellular lipid storage occurs in skeletal muscle of both athletes and type 2 diabetes patients (T2D) but their metabolic phenotypes are at opposite ends of insulin sensitivity and cardiometabolic risk. Hypothesis: Intramyocellular lipid saturation and flux are determinants of insulin resistance. Methods: Age-matched athletes (n=28) and T2D (n=27) underwent 1 H-magnetic resonance spectroscopy for analysis of saturated (fSL) and unsaturated lipid (fUL) fractions of vastus lateralis, blood lipids, glucose and insulin sensitivity, skeletal muscle biopsy for lipidomics/insulin signalling, cardiopulmonary exercise peak VO 2 and intravenous administration of stable isotopes of [U- 13 C]-palmitate and -linoleate for skeletal muscle saturated/unsaturated fatty acid fluxes (fractional synthesis rate, FSR). Tests were performed at baseline and after controlled insulin sensitivity changes (4-week athletes deconditioning and endurance exercise training at ≥65% of baseline peakVO 2, 5 hours/week x 8 weeks in T2D). Results: We demonstrate higher intramyocellular fSL and lower fUL in athletes compared to T2D (p=0.0004). Trained athletes have a 4-fold (palmitate) and 2.2-fold (linoleate) higher FSR compared to T2D (p=0.005 and 0.006, respectively). Athletes’ deconditioning results in reductions in skeletal muscle lipid saturation, palmitate and linoleate FSR. Conversely, 8-week endurance training of T2D results in intramyocellular lipid saturation increase (p&lt;0.0001) as well as a relatively larger (2.2-fold) palmitate FSR increase (p=0.04) than the 1.8-fold linoleate FSR increase (p=0.03), re-aligning the T2D skeletal muscle phenotype to that of deconditioned athletes. These adaptations were synchronous with significant insulin sensitivity improvement (p&lt;0.05), decrease in serum cholesterol (p=0.02) and triglycerides (p=0.0005), improved glycaemic control (HBA1c, p=0.0003), increased peak VO 2 (p&lt;0.0001) and upregulation of skeletal muscle phosphorylated AKT (p=0.01) and AMPK (p=0.005) in T2D. Conclusions: Maladapted intramyocellular lipid storage and fluxes in T2D patients show reversibility after endurance training through increased contributions of the saturated fatty acids pools.
Primary central nervous system lymphoma
Authors: Andrés J. M. Ferreri, Teresa Calimeri, Kate Cwynarski, Jorg Dietrich, Christian Grommes, Khê Hoang-Xuan, Leland S. Hu, Gerald Illerhaus, Lakshmi Nayak, Maurilio Ponzoni, Tracy T. Batchelor
Journal: Nature Reviews Disease Primers (2023)
Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs
Authors: Jacqueline P. Ernest, Janice Jia Ni Goh, Natasha Strydom, Qianwen Wang, Rob C. van Wijk, Nan Zhang, Amelia Deitchman, Eric Nuermberger, Rada M. Savic
Journal: European Respiratory Journal (2023)

Background: Phase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum CFU over 14 days, as the primary end-point for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from USD 7 million to USD 19.6 million on average, while &gt;30% of drugs fail to progress to phase 3. Better utilising pre-clinical data to predict and prioritise the most likely drugs to succeed will thus help to accelerate drug development and reduce costs. We aim to predict clinical EBA using pre-clinical in vivo pharmacokinetic (PK)-pharmacodynamic (PD) data and a model-based translational pharmacology approach. Methods and findings: First, mouse PK, PD and clinical PK models were compiled. Second, mouse PK-PD models were built to derive an exposure–response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PK-PD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations. Conclusion: This platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.
Whether cryosurgery for oral premalignant lesions influences the outcome of malignant transformation
Authors: Wei Liu, Xiaochen Zhang, Linjun Shi, Xuemin Shen
Journal: International Journal of Surgery (2023)

aDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China bCollege of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China cDepartment of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai 200011, China. Tel.: +86 21 23271699. E-mail address: [email protected] (X. Zhang). *Corresponding authors. Address: Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai 200011, China. Tel.: +86 21 63162851. E-mail address: [email protected] (L. Shi). *Corresponding Author. Address: Shanghai Jiao Tong University School of Medicine CHINA. E-mail address: [email protected] (X. Shen). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0/
Risk factors of epidural hematoma in patients undergoing spinal surgery: a meta-analysis of 29 cohort studies
Authors: Mingjiang Luo, Qi Cao, Zhiming Zhao, Yuxin Shi, Qilong Yi, Jiang Chen, Xin Zeng, Zhongze Wang, Haoyun Wang, Yuxin Yang, Juemiao Chen, Gaigai Yang, Beijun Zhou, Can Liang, Ridong Tan, Di Wang, Siliang Tang, Jinshan Huang, Zhihong Xiao, Zubing Mei
Journal: International Journal of Surgery (2023)

Objective We conducted this meta-analysis to identify risk factors for spinal epidural hematoma (SEH) among patients following spinal surgery. Methods We systematically searched PubMed, Embase, and the Cochrane Library for articles that reported risk factors associated with the development of SEH in patients undergoing spinal surgery from inception to July 2, 2022. The pooled OR was estimated using a random-effects model for each investigated factor. The evidence of observational studies was classified as high-quality (Class I), moderate-quality (Class II or III) and low-quality (Class IV) based on sample size, Egger’s P value and between-study heterogeneity. In addition, subgroup analyses stratified by study baseline characteristics and leave-one-out sensitivity analyses were performed to explore the potential sources of heterogeneity and the stability of the results. Results Of 21791 articles screened, 29 unique cohort studies comprising 150,252 patients were included in the data synthesis. Studies with high-quality evidence showed that older patients (≥60 y) (OR, 1.35; 95% CI, 1.03-1.77) were at higher risk for SEH. Studies with moderate-quality evidence suggested that patients with a BMI ≥25 kg/m² (OR, 1.39; 95% CI, 1.10-1.76), hypertension (OR, 1.67; 95% CI, 1.28-2.17), and diabetes (OR, 1.25; 95% CI, 1.01-1.55) and those undergoing revision surgery (OR, 1.92; 95% CI, 1.15-3.25) and multilevel procedures (OR, 5.20; 95% CI, 2.89-9.37) were at higher risk for SEH. Meta-analysis revealed no association between tobacco use, operative time, anticoagulant use or American Society of Anesthesiologists (ASA) classification and SEH. Conclusions Obvious risk factors for SEH include four patient-related risk factors, including older age, obesity, hypertension, and diabetes, and two surgery-related risk factors, including revision surgery and multilevel procedures. These findings, however, must be interpreted with caution because most of these risk factors had small effect sizes. Nonetheless, they may help clinicians identify high-risk patients to improve prognosis.
HIV and immunotherapy: will CAR-T cell therapy cure HIV?
Authors: Vishnu Priya Veeraraghavan, Jyotsna Needamangalam Balaji, Sreenidhi Prakash, Lavina Prashar, Ullas Mony, Krishna Mohan Surapaneni
Journal: International Journal of Surgery (2023)

Veeraraghavan, Vishnu Priya PhD; Needamangalam Balaji, Jyotsna MBBS; Prakash, Sreenidhi MBBS; Prashar, Lavina MBChB. MD; Mony, Ullas PhD; Surapaneni, Krishna Mohan PhD, MHPE, FRSC Author Information
Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: an updated systematic review and meta-analysis
Authors: Dieuwke Luijten, Rosa Talerico, Stefano Barco, Suzanne C. Cannegieter, Marion Delcroix, Yvonne M. Ende-Verhaar, Menno V. Huisman, Stavros Konstantinidis, Albert T.A. Mairuhu, Thijs E. van Mens, Maarten Ninaber, Piotr Pruszczyk, Anton Vonk Noordegraaf, Frederikus A. Klok
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The weighted pooled CTEPH incidence in PE survivors was 2.7%. RV dysfunction at the moment of the acute PE, unprovoked PE and/or recurrent VTE are associated with an increased CTEPH incidence.</b> https://bit.ly/3Nd8GC0
Evolution of faecal microbiome diversity in long-term care residents during an antimicrobial stewardship programme and its association with multidrug-resistant bacterial colonisation
Authors: Claudio Alba-Rubio, Germán Peñalva-Moreno, Tania Cebrero-Cangueiro, Gema Labrador-Herrera, Juan Carlos Crespo-Rivas, Ana Belén Guisado-Gil, Ángel Rodríguez-Villodres, Julio Cerillo-Matilla, Bárbara Cachero-Alba, Josefa Gil-Moreno, María Isabel Galvá-Borras, Mercedes García-Moreno, José Antonio Lepe, María Eugenia Pachón-Ibáñez, José Miguel Cisneros
Journal: Journal of Infection (2023)
Shorter duration of antibiotic therapy for exacerbation of COPD
Authors: Victor Leung, Colin Lee
Journal: European Respiratory Journal (2023)

We would like to thank the authors of the recently released Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report and express one area of concern related to the general recommendation for 5- to 7-day antibiotic therapy duration [1]. We believe the totality of evidence supports a shorter course (5 days or less) for treating mild to moderate exacerbations of COPD (ECOPD). Although longer courses of antibiotics have traditionally been recommended for many infections, the basis for this originated from dogma versus rigorous trial evidence [2]. Excessive antibiotic durations are not sustainable in the face of increasing antibiotic resistance, one of the top global public health threats. Highlighting the evidence that supports a more explicit statement recommending shorter duration of antibiotics for exacerbation of COPD http://bit.ly/3KmLmQR
Can we call all obstructive lung diseases COPD?
Authors: Hyun Lee, Sun Hye Shin, Hye Yun Park, Seong Yong Lim
Journal: European Respiratory Journal (2023)

The executive summary of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report was recently published in the European Respiratory Journal [1]. While major revisions were made across all chapters, we are very interested in the revised COPD definition and newly defined taxonomy (etiotypes). Can all chronic airway infections that lead to airflow obstruction be regarded as COPD-I? <https://bit.ly/3nCod3K>
Incidence and time to development of malignancies arising on the scalp of patients with erosive pustular dermatosis based on sex: A retrospective analysis
Authors: Norhan Shamloul, Payvand Kamrani, Gelan Shamloul, Allen Kunselman, Diane Thiboutot, Elizabeth Billingsley, Charlene Lam
Journal: Journal of the American Academy of Dermatology (2023)
Prevalence and implications of mogamulizumab-induced immune-related adverse events in mycosis fungoides/Sézary syndrome; a single-center experience
Authors: Abdulhadi Jfri, Cesar A. Virgen, Marianne Tawa, Anita Giobbie-Hurder, Thomas S. Kupper, David C. Fisher, Nicole R. LeBoeuf, Cecilia Larocca
Journal: Journal of the American Academy of Dermatology (2023)